松弛素抑制氧化应激反应保护小鼠心肌微血管内皮细胞的缺氧/ 复氧损伤.

BACKGROUND: Serelaxin is a recombinant form of human relaxin 2. As endogenous anti-fibrosis active substances, serelaxin may relieve the symptoms and improve the prognosis of patients with acute heart failure. However, there is no report on the effect of serelaxin on hypoxia/reoxygenation injury of myocardial microvascular endothelial cells (H5V) in mice through regulating oxidative stress. OBJECTIVE: To investigate the role on serelaxin in a model of hypoxia/reoxygenation-induced mouse cardiac microvascular endothelial cells (H5V)injury. METHODS: To establish a mouse H5V hypoxia/reoxygenation injury model, cells were incubated under hypoxia for 3, 6, and 12 hours followed by 3 hours of reoxygenation. The optimal time of cellular hypoxia/reoxygenation was determined by cell viability and lactate dehydrogenase activity assay. Different concentrations of serelaxin (0, 60, 100, 140, 180 ng/mL) were selected to act in the H5V cellular hypoxia/reoxygenation injury model, and the optimal drug concentration for drug treatment of cellular hypoxia-reoxygenation injury was determined by the cell viability and lactate dehydrogenase activity assays. H5V cells were then divided into three groups: control, model (hypoxia/reoxygenation), and serelaxin (hypoxia/reoxygenation+180 ng/mL serelaxin) groups. Malondialdehyde, superoxide dismutase and reactive oxygen species levels were detected in each group. RESULTS AND CONCLUSION: Compared with the control group, cell proliferation was significantly reduced after hypoxia 6 hours/reoxygenation 3 hours and hypoxia 12 hours/reoxygenation 3 hours (P < 0.05), while the lactate dehydrogenase activity in cell supernatant was significantly increased (P < 0.05). Therefore, cells cultured under hypoxia 6 hours/reoxygenation 3 hours were selected for subsequent experiments. Cell viability was significantly increased in the serelaxin group compared with the model group (P < 0.05), while the lactate dehydrogenase activity in cell supernatant was significantly decreased (P < 0.05). Therefore, 180 ng/mL serelaxin was selected for subsequent experiments. Compared with the model group, the serelaxin group showed a significant decrease in reactive oxygen species and malondialdehyde levels but a significant increase in the level of superoxide dismutase (all P < 0.05). To conclude, H5V cells subjected to hypoxia 6 hours/reoxygenation 3 hours could establish a model of H5V vascular endothelial cell injury, and 180ng/mL serelaxin could improve the cell viability and anti-oxidative stress ability. [ABSTRACT FROM AUTHOR]